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Liver X receptor agonist prevents the evolution of collagen-induced arthritis in mice

 Min-Chan Park  ;  Yong-Jin Kwon  ;  Soo-Jin Chung  ;  Yong-Beom Park  ;  Soo-Kon Lee 
 RHEUMATOLOGY , Vol.49(5) : 882-890, 2010 
Journal Title
Issue Date
Animals ; Arthritis, Experimental/metabolism* ; Arthritis, Experimental/prevention & control ; Benzoates/metabolism* ; Benzylamines/metabolism* ; Cattle ; Cells, Cultured ; Cytokines/metabolism* ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Inflammation Mediators/metabolism* ; Liver X Receptors ; Mice ; Mice, Inbred DBA ; Orphan Nuclear Receptors/agonists* ; Orphan Nuclear Receptors/metabolism
Rheumatoid arthritis ; Liver X receptors ; GW3965 ; Collagen-induced arthritis
OBJECTIVE: Liver X receptors (LXRs) have been characterized as regulators of macrophage inflammatory pathways. Synthetic LXR agonists inhibit the macrophage response to bacterial pathogens and antagonize the induction of a number of pro-inflammatory genes. The aim of this study was to investigate the preventive effects of synthetic LXR agonist, GW3965, treatment on the evolution of arthritis and inflammatory response in a murine CIA model. METHODS: Intradermal injection of bovine type II CIA in DBA/1 mice. Along with the induction of CIA, mice were treated with oral GW3965 (0.1, 0.3 or 1.0 mg/kg/day) or vehicle from Day 1 to Day 40. Clinical assessment for arthritis scores and histopathological assessment of joint sections were performed. The expression of inflammatory mediators was evaluated by immunohistochemical staining. Serum pro-inflammatory cytokine levels were determined using ELISA. RESULTS: The CIA incidence was 100% on Day 27 and the severity progressed until Day 35 with histological features of cartilage erosion in vehicle-treated mice. GW3965 treatment significantly reduced the arthritis incidence and attenuated the clinical and histological severity, compared with vehicle-treated mice. GW3965 treatment also significantly reduced inflammatory mediator production in joint sections and serum pro-inflammatory cytokine levels in a dose-dependent manner. CONCLUSIONS: These results indicate that activation of LXRs suppresses the onset of CIA and reduces inflammation and joint destruction in CIA mice. The data could suggest that LXR treatment is an effective prophylactic approach to suppress the evolution of synovitis and resultant joint destruction observed in RA.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Min Chan(박민찬) ORCID logo https://orcid.org/0000-0003-1189-7637
Park, Yong Beom(박용범)
Lee, Soo Kon(이수곤)
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